Rush University Medical Center

About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.

REST and stress resistance in ageing and Alzheimer’s disease

Abstract: Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain. REST, a developmental regulator, is markedly induced in human neurons during ageing but is lost in Alzheimer’s disease; REST represses genes that promote neurodegeneration, is neuroprotective in animal models, and is associated with cognitive preservation and longevity in humans. Age is the biggest risk factor for neurodegenerative disease. But why do some age with cognitive function intact, yet others decline and develop Alzheimer's disease? Here Bruce Yankner and colleagues show that during ageing, a protein known as REST (repressor element 1-silencing transcription factor, also called NRSF) is increasingly expressed in human cortical and hippocampal neurons. REST levels are strongly correlated with cognitive preservation and longevity. REST represses genes that promote cell death and Alzheimer's disease pathology and induces those that mediate the stress response. Moreover, REST protects neurons from oxidative stress and amyloid β-protein toxicity. Deleting REST from the mouse brain results in age-related neuronal cell death. And, in humans with mild cognitive impairment or Alzheimer's disease, REST is excluded from the nucleus in neurons, and this exclusion is associated with autophagy and misfolded proteins. This work suggests that the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

Oral appliances for snoring and obstructive sleep apnea: a review.

Abstract: We conducted an evidence-based review of literature regarding use of oral appliances (OAs) in the treatment of snoring and obstructive sleep apnea syndrome (OSA) from 1995 until the present. Our structured search revealed 141 articles for systematic scrutiny, of which 87 were suit- able for inclusion in the evidence base, including 15 Level I to II random- ized controlled trials and 5 of these trials with placebo-controlled treat- ment. The efficacy of OAs was established for controlling OSA in some but not all patients with success (defined as no more than 10 apneas or hypopneas per hour of sleep) achieved in an average of 52% of treated patients. Effects on sleepiness and quality of life were also demonstrated, but improvements in other neurocognitive outcomes were not consistent. The mechanism of OA therapy is related to opening of the upper airway as demonstrated by imaging and physiologic monitoring. Treatment ad- herence is variable with patients reporting using the appliance a median of 77% of nights at 1 year. Minor adverse effects were frequent whereas major adverse effects were uncommon. Minor tooth movement and small changes in the occlusion developed in some patients after prolonged use, but the long-term dental significance of this is uncertain. In comparison to continuous positive airway pressure (CPAP), OAs are less efficacious in reducing the apnea hypopnea index (AHI), but OAs appear to be used more (at least by self report), and in many studies were preferred over CPAP when the treatments were compared. OAs have also been com- pared favorably to surgical modification of the upper airway (uvulopalato- pharyngoplasty, UPPP). Comparisons between OAs of different designs have produced variable findings. The literature of OA therapy for OSA now provides better evidence for the efficacy of this treatment modality and considerable guidance regarding the frequency of adverse effects and the indications for use in comparison to CPAP and UPPP. Citation: Ferguson KA; Cartwright R; Rogers R et al. Oral Appliances for Snoring and Obstructive Sleep Apnea: A Review. SLEEP 2006;29(2): 244-262.

Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease.

Abstract: Brain-derived neurotrophic factor (BDNF) is critical for the function and survival of neurons that degenerate in the late stage of Alzheimer's disease (AD). There are two forms of BDNF, the BDNF precursor (proBDNF) and mature BDNF, in human brain. Previous studies have shown that BDNF mRNA and protein, including proBDNF, are dramatically decreased in end-stage AD brain. To determine whether this BDNF decrease is an early or late event during the progression of cognitive decline, we used western blotting to measure the relative amounts of BDNF proteins in the parietal cortex of subjects clinically classified with no cognitive impairment (NCI), mild cognitive impairment (MCI) or mild to moderate AD. We found that the amount of proBDNF decreased 21 and 30% in MCI and AD groups, respectively, as compared with NCI, consistent with our previous results of a 40% decrease in end-stage AD. Mature BDNF was reduced 34 and 62% in MCI and AD groups, respectively. Thus, the decrease in mature BDNF and proBDNF precedes the decline in choline acetyltransferase activity which occurs later in AD. Both proBDNF and mature BDNF levels were positively correlated with cognitive measures such as the Global Cognitive Score and the Mini Mental State Examination score. These results demonstrate that the reduction of both forms of BDNF occurs early in the course of AD and correlates with loss of cognitive function, suggesting that proBDNF and BDNF play a role in synaptic loss and cellular dysfunction underlying cognitive impairment in AD.

Duration of menopausal vasomotor symptoms over the menopause transition.

Abstract: Importance The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. Objectives To determine total duration of frequent VMS (≥6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. Design, Setting, and Participants The Study of Women’s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. Main Outcomes and Measures Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. Results The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. Conclusions and Relevance Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.